title: Nociceptive and inflammatory responses induced by formalin in the orofacial region of rats: effect of anti-TNFalpha strategies.
abstract: This study evaluated the effects of different anti-TNFalpha strategies on the nociceptive and inflammatory responses triggered by formalin in the rat orofacial region. Formalin injection (2.5%) into the right upper lip caused a nociceptive response that was biphasic, with the first phase observed between 0 and 3 min and the second phase between 12 and 30 min. Plasma extravasation induced by formalin was time-related and reached the peak at 360 min. The monoclonal antibody anti-TNFalpha (25 and 50 pg/lip) significantly inhibited the second phase of formalin-induced nociceptive behavior, while the first phase remained unaltered. The systemic treatment with the chimeric anti-TNFalpha antibody infliximab also caused a significant inhibition of the second phase. Interestingly, the local administration of infliximab (50 pg/lip) produced a significant reduction of both phases of formalin-induced nociception. In addition, the systemic pretreatment with the preferential inhibitor of TNFalpha synthesis thalidomide (25 and 50 mg/kg, p.o) promoted a marked reduction of the first and second phases of formalin-evoked nociception. The local administration of the monoclonal antibody anti-TNFalpha (25 and 50 pg/lip) or infliximab (50 pg/lip) markedly reduced the plasma extravasation induced by formalin. Otherwise, formalin-elicited plasma extravasation was not significantly affected by the systemic administration of either infliximab (1 mg/kg; s.c) or thalidomide (50 mg/kg, p.o). Present data suggest that blocking TNFalpha effects, through different pharmacological tools, could represent a good alternative to control orofacial inflammatory pain that is refractory to other drugs.
authors.affiliation: School of Pharmacy, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.
authors.forename: Paula Juliana
authors.initials: PJ
authors.lastname: Seadi Pereira
authors.forename: Fabiana
authors.initials: F
authors.lastname: Noronha Dornelles
authors.forename: Diógenes
authors.initials: D
authors.lastname: Santiago Santos
authors.forename: João
authors.initials: J
authors.lastname: Batista Calixto
authors.forename: Fernanda
authors.initials: F
authors.lastname: Bueno Morrone
authors.forename: Maria Martha
authors.initials: MM
authors.lastname: Campos
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D005157:Facial Pain / Q000139:chemically induced* / Q000473:pathology* / Q000523:psychology; D005557:Formaldehyde / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D000069285:Infliximab; D007267:Injections; D008046:Lip; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D005557:Formaldehyde; D013792:Thalidomide; D000069285:Infliximab